Palladium (II) Precursors for Clean in situ Formation of Ad Hoc Cross‐Coupling Catalysts: their Application in One‐pot/Two‐step Catalyses with 2‐Biaryl‐dialkylphosphine Ligands

Complexes <i>cis</i>‐[Pd(Ar^F)₂(NCMe)₂] (<b>A</b>) and <i>cis</i>‐[Pd(Ar^F)2(THF)₂] (<b>B</b>) are fast general precursors easy to prepare, store and handle, which allow <i>in situ</I> synthesis of tailor‐made [Pd(Ar)(X)(L)] catalysts for chosen <b>Ar‐Nu</b> coupling, provided that the L ligand (in this case PR₂(2‐biaryl)) induces (C₆F₃H₂)₂ coupling. This fluorinated byproduct is inert in the reaction conditions, and no other is expected because the Ar and X groups are the same in the catalyst, the intermediates and the products. The application of <b>A</b> or <b>B</b> in catalysis (<i>e.g.</i> with 1% catalyst ratio) consists of a first step (formation of 1% tailor‐made catalyst) where 100 ArX + 1 <b>A</b> (or <b>B</b>) + 1 L in THF gives a solution with 99 ArX + 1 [Pd(Ar)(X)(L)] + (Ar^F)₂. The only other byproduct is THF or NCMe. In the second step, addition of the nucleophile, 100 Q(Nu), triggers and completes the catalytic cycle yielding 100 Ar‐Nu + 100 Q(Br) + 1 [Pd0(L)]. The 100% yield is theoretical, but the tested catalysis (Ar–Me Negishi coupling, C₆F₅–alkynyl Stille coupling and Ar‐naphthyl Suzuki coupling) using <b>B</b> as precursor, SPhos as ligand, and 1000:1 reagents:catalyst ratio, afford 95‐99% yield. In contrast, aryl‐amination requires 1000:5 ratio to give 96% yield (or 1000:50 for 99% yield) because PhNH₂ eventually blocks the catalyst. As a bonus, the presence of F in the precursors facilitates stepwise ¹⁹F NMR monitoring of formation of the [Pd(Ar)(X)(L)] catalyst with different phosphines, facilitating analysis of weaknesses or strengths of each of them to produce the catalyst, and helps in the choice of the most convenient one for the case. The <i>in situ</i> catalyst formation is ideal for serial two‐step catalysis with different phosphines or different nucleophiles.